Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy
Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/21/6498 |
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| author | Michele Montori Chiara Scorzoni Maria Eva Argenziano Daniele Balducci Federico De Blasio Francesco Martini Tiziana Buono Antonio Benedetti Marco Marzioni Luca Maroni |
| author_facet | Michele Montori Chiara Scorzoni Maria Eva Argenziano Daniele Balducci Federico De Blasio Francesco Martini Tiziana Buono Antonio Benedetti Marco Marzioni Luca Maroni |
| author_sort | Michele Montori |
| collection | DOAJ |
| description | Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis. For instance, a better prognosis is associated with IL-33 expression and low stromal IL-6 (whose secretion is stimulated by microRNA). In contrast, a worst prognosis is given by the expression of PDGF-D, podoplanin, SDF-1, α-SMA high expression, and periostin. The maturity phenotype has a prognostic relevance too. New therapeutic strategies involving CAFs are currently under study. Promising results are obtained with anti-PlGF therapy, nintedanib (BIBF1120), navitoclax, IPI-926, resveratrol, and controlled hyperthermia. |
| first_indexed | 2024-03-09T18:57:24Z |
| format | Article |
| id | doaj.art-23072d3f469643eda01c293d30032baf |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T18:57:24Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-23072d3f469643eda01c293d30032baf2023-11-24T05:18:40ZengMDPI AGJournal of Clinical Medicine2077-03832022-11-011121649810.3390/jcm11216498Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for TherapyMichele Montori0Chiara Scorzoni1Maria Eva Argenziano2Daniele Balducci3Federico De Blasio4Francesco Martini5Tiziana Buono6Antonio Benedetti7Marco Marzioni8Luca Maroni9Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyClinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica delle Marche, 60126 Ancona, ItalyCholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis. For instance, a better prognosis is associated with IL-33 expression and low stromal IL-6 (whose secretion is stimulated by microRNA). In contrast, a worst prognosis is given by the expression of PDGF-D, podoplanin, SDF-1, α-SMA high expression, and periostin. The maturity phenotype has a prognostic relevance too. New therapeutic strategies involving CAFs are currently under study. Promising results are obtained with anti-PlGF therapy, nintedanib (BIBF1120), navitoclax, IPI-926, resveratrol, and controlled hyperthermia.https://www.mdpi.com/2077-0383/11/21/6498CAFcancer-associated fibroblastcholangiocarcinomadesmoplasiaα-SMAstroma |
| spellingShingle | Michele Montori Chiara Scorzoni Maria Eva Argenziano Daniele Balducci Federico De Blasio Francesco Martini Tiziana Buono Antonio Benedetti Marco Marzioni Luca Maroni Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy Journal of Clinical Medicine CAF cancer-associated fibroblast cholangiocarcinoma desmoplasia α-SMA stroma |
| title | Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy |
| title_full | Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy |
| title_fullStr | Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy |
| title_full_unstemmed | Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy |
| title_short | Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy |
| title_sort | cancer associated fibroblasts in cholangiocarcinoma current knowledge and possible implications for therapy |
| topic | CAF cancer-associated fibroblast cholangiocarcinoma desmoplasia α-SMA stroma |
| url | https://www.mdpi.com/2077-0383/11/21/6498 |
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